Novel Forms of Osteogenesis Imperfecta:
Types V & VI

Osteogenesis Imperfecta (OI) is a heritable disease of bone, characterized by low bone mass and bone fragility. According to the generally accepted Sillence classification, the disease has been divided into four types, based on clinical and radiographic features as well as disease severity. OI type I is a mild form of the disease, while OI type II is almost always fatal in the perinatal period. OI type III is a severe form, with progressive deformity in the absence of surgical intervention. Patients with OI type IV are moderately to severely affected. The underlying genetic defect in the majority of patients with OI is attributable to mutations in one of two genes which encode the major structural protein of bone, called type I collagen.

For a number of years, investigators in Montreal have been doing special studies on the histology of OI bone, categorizing the appearance of the different Sillence types of OI bone under the microscope. They noticed that some patients who are clinically within the Sillence type IV group of patients had a distinct histology pattern to their bone. When they reviewed the full clinical presentation of these patients, they found that groups of patients had other features in common. They named these groups types V and VI OI. This classification continues the numbering of the Sillence classification, but is diagnostically based on histology rather than on the same criteria used for types I-IV. Patients in these two groups do not have evidence of having mutations in the type I collagen genes.

Patients with OI type V demonstrate three findings (the OI type V "triad"). The first is a dense band adjacent to the growth plate of the long bones, which can be seen on x-rays. The second feature is the development of unusually large calluses, called hypertrophic calluses, at the sites of fractures or surgical procedures. A callus is an area of new bone that is laid down at the fracture site as part of the healing process. Finally, patients with OI type V have calcification of the membrane between the radius and ulna, the bones of the forearm. This leads to restriction of forearm rotation, and patients may note that it is difficult to open a door by rotating the wrist. Instead, they must rotate the entire arm to achieve such a movement. In addition to this OI type V triad, patients have white sclerae and normal teeth. The bone has a "mesh-like" appearance when viewed under the microscope. OI type V is dominantly inherited, which means that if a parent has the condition, there is a 50% chance that it could be passed onto a subsequent child. The underlying genetic defect in OI type V is presently unknown.

Patients with OI type VI are more difficult to identify from physical features or x-rays. These patients are moderately to severely affected. They have normal (white or slightly blue) sclerae and the teeth are not affected. The alkaline phosphatase (an enzyme linked to bone forming cell activity) activity level is slightly elevated in OI type VI, and this can be determined by a blood test. Because the clinical features are so similar to other moderate forms of OI, a bone biopsy is the only method by which OI type VI can be diagnosed with certainty. The bone from patients with this form has a distinctive "fish-scale" appearance when viewed under the microscope. Eight patients with this bone histology have been identified. None of these patients have affected parents and none have had children. Thus, the inheritance of OI type VI is unknown. As in OI type V, the genetic basis for OI type VI remains to be determined, but there is no evidence of Type I collagen abnormalities.

Patients with type V and VI OI have received bisphosphonates. Numbers are currently too small to draw conclusions, but it appears that type V patients rapidly increase bone density, while Type VI do so much less evidently. The specific bone lesions in type VI may explain that difference.

The original scientific references for these types are listed below:

Glorieux, F.H., Rauch, F., Plotkin, H., Ward, L., Travers, R., Roughley, PJ., Lalic, L., Glorieux, D.F., Fassier, F. and Bishop, N.J. Type V Osteogenesis Imperfecta: A new form of brittle bone disease. J Bone Min Res, 15:1650-1658, 2000.

Glorieux FH, Ward LM, Rauch F, Lalic L, Roughley PJ, Travers R. Osteogenesis Imperfecta Type VI: A Form of Brittle Bone Disease with a Mineralization Defect. J Bone Miner Res, 17: 30-38, 2002.

The investigators who have described types V and VI OI can be contacted for further information:

Francis H. Glorieux, MD, PhD
Director of Research
E-mail: glorieux@shriners.mcgill.ca

Frank Rauch, MD
Assistant Director of Clinical Research
E-mail: frauch@shriners.mcgill.ca 

Address:

Shriners Hospital for Children
1529 Cedar Avenue
Montréal, Québec, Canada
H3G 1A6

Telephone: 514 842 5964.

 


This information is brought to you by the
NIH Osteoporosis and Related Bone Diseases~National Resource Center (ORBD~NRC)
and the Osteogenesis Imperfecta Foundation

National Institutes of Health
 Osteoporosis and Related Bone Diseases
 National Resource Center
1232 22nd St., NW
Washington, DC 20037-1292
Tel: 800/624-BONE or 202/223-0344
Fax: 202/293-2356, TYY: 202/466-4315
http://www.osteo.org
E-mail: orbdnrc@nof.org

The National Resource Center is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with contributions from the National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, National Institute of Environmental Health Sciences, NIH Office of Research on Women's Health, Office of Women's Health, PHS, and the National Institute on Aging. The Resource Center is operated by the National Osteoporosis Foundation, in collaboration with the Paget Foundation and the Osteogenesis Imperfecta Foundation.


10/02

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